Lactic Acidosis During Entecavir(ETV)Treatment

NCT01354652 | Terminated Phase 4 Results DMC

• 1 other identifier: Hanchu3915
• Study Type: interventional
• Target: 5
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to investigate whether entecavir treatment increases the incidence of lactic acidosis compared to another nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), lamivudine, and/or no NRTI treatment, in patients with cirrhosis or hepatic failure whose Model for End stage Liver Disease (MELD) scores are over 18.

Conditions

Lactic Acidosis

Keywords

lactic acidosis; entecavir; lamivudine

Outcome Measures

Primary Outcomes (1)

• Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L of Any Etiology

  incidence of elevated venous lactate levels more than 2 mmol/L of any etiology until development of lactic acidosis, orthotropic liver transplantation (OLT), death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

  participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Secondary Outcomes (5)

• Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L Directly Related to NRTI

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

• Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L Caused by Etiologies Other Than NTRIs

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

• Frequency of Concomitant Prescribed Medications Possibly Associated With Lactic Acidosis Other Than NTRIs

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

• Arterial pH and Anion Gap in Cases With Elevated Blood Lactate Levels (at the Time of Detection and Peak Levels

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

• Overall OLT-free Survival

  Participants will be followed for the duration of hospital stay or outpatients visit, an expected average of 12 months

Study Arms (3)

entecavir

EXPERIMENTAL

Oral 0.5mg/day until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Drug: entecavir, lamivudine

lamivudine

ACTIVE COMPARATOR

Oral 100mg/day lamivudine until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Drug: entecavir, lamivudine

no NRTI group

NO INTERVENTION

hepatitis C virus associated LC patients for the calculation of lactic acidosis incidence

Interventions

entecavir, lamivudine DRUG

entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Also known as: Entecavir:baraclude, Lamivudine: zeffix

entecavir; lamivudine

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• and more than 18 years, and less than 65 years
• HBV-related liver cirrhosis or acute-on-chronic liver failure
• Prior documentation of chronic HBV infection at least 6 months before randomization
• MELD score 18 and more than 18
• Venous blood lactate level 2 and less than 2 mmol/L

You may not qualify if:

• Age of 65 or older, or younger than 18
• Patients with acute hepatitis B including acute liver failure
• Acute-on-chronic liver failure precipitated by acute hepatitis A or acetaminophen intoxication
• MELD score less than 18
• entecavir, lamivudine, telbivudine, clevudine, adefovir or tenofovir treatment continued longer than 3 months before entry.
• Evidence of genotypic or virological resistance to lamivudine, clevudine, telbivudine, or adefovir
• Patients with elevated venous blood lactate levels more than 2 mmol/L
• Recent episodes of active infection, hypotension (systolic blood pressure less than 90 mmHg), gastrointestinal or other active bleeding within 2 weeks before entry
• Any alcohol intake within 2 weeks before entry
• Recent use of acetaminophen, epinephrine, metformin, iron, isoniazid, propofol, salicylate, sulfasalazine, or valproic acid within 2 weeks before entry. Use of lactulose is permitted.
• Presence of hepatocellular carcinoma. Patients with hepatocellular carcinoma meeting the Milan criteria can be permitted.
• Any cancer other than hepatocellular carcinoma except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis \& T1). Any cancer curatively treated at least 3 years prior to entry is permitted.
• Patients with HIV infection
• Female patients in pregnancy
• for no NRTI group

Sponsors & Collaborators

• Asan Medical Center: lead

MeSH Terms

Conditions

Acidosis, Lactic

Interventions

entecavir; Lamivudine

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: Dr. Han Chu Lee
• Organization: AsanMC

hch@amc.seoul.kr

82230103915

Study Officials

• Han Chu Lee, M.D

  Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: May 17, 2011
• Study Start: May 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: May 9, 2018
• Results First Posted: February 20, 2015

Record last verified: 2018-04